Since our discovery, published in 1965, that macromolecular binding of radioactivity from labeled cortisol could be an intermediate step in the hormonal induction of liver enzymes, like tyrosine aminotransferase, we have provided evidence for 6 proteins, including the hormone receptor, in liver cytosol which bind glucocorticoids or their anionic metabolites (primarily mono- and disulfates). This application for continued support is sought for research focused to three of these proteins: the glucocorticoid receptor, ligandin and a new glucocorticoid anion-binding protein. Proposed work with the hormone receptor involves the mechanism of its activation accounting for specific changes in the steroid-receptor complex enabling it to bind to cell nuclei, chromatin or DNA. Experiments with cell culture systems are also outlined which may lead to the mapping of the gene for the glucocorticoid receptor and to any regulatory genes. Liver and kidney dexamethasone receptors will be compared to determine if there are isoreceptors in different tissues of the same animal. Induction of ligandin by phenobarbital in vivo and in vitro will utilize ligandin mRNA. Experiments are described which may lead to the chromosomal assignment of the gene for ligandin and any regulatory genes. A new corticosteroid anion binding protein will be isolated, characterized and its physiological function sought. These studies will extend previous work and direct certain future investigations towards genetic controls through cell culture studies and somatic cell genetics.